BOSTON – Although the risk of osteonecrosis of the jaw is low in patients using oral bisphosphonates, patients should be aware of treatment risks associated with this class of drugs.
Clinicians should still do their best to educate patients on risks and on preventive care measures, said Meryl S. LeBoff MD, associate professor, Harvard Medical School, and director of the Skeletal Health and Osteoporosis Program and Bone Density Unit in the endocrine, diabetes, and hypertension division of Brigham and Women’s Hospital. LeBoff spoke at the Endocrine Society’s 88th Annual Meeting.
“We don’t really know the true incidence of [osteonecrosis of the jaw] either in association with the use of the oral or the intravenous bisphosphonates,” LeBoff told Endocrine Today. “Many are cases that have been reported to the pharmaceutical companies or in published series or in retrospective analyses since the drugs were approved.” While there are about 191 million prescriptions of oral bisphosphonates worldwide, there are about 170 cases of osteonecrosis of the jaw reported with alendronate therapy and about 20 cases with risedronate.
“This is quite a low rate, although clearly the diagnoses have to be examined and adjudicated in each of these cases,” LeBoff said.
Uniform diagnostic criteria for osteonecrosis of the jaw exist, LeBoff said.
“We don’t fully understand the mechanisms and how prevention is best achieved — what optimal bisphosphonate regimens are for patients who do have malignancies, to decrease skeletal events,” LeBoff said.
LeBoff summarized a study conducted by Sook-Bin Woo et al., from the May 2006 issue of Annals of Internal Medicine.
The study examined 368 case reports of osteonecrosis of the jaw. Ninety-four percent of those patients were treated with IV bisphosphonates such as pamidronate disodium (Aredia, Novartis) and zoledronic acid (Zometa, Novartis). Eighty-five percent of patients had multiple myeloma or metastic breast cancer.
Four percent of patients in the study treated for osteoporosis had osteonecrosis of the jaw.
“Overall, in the osteoporosis patients, they’re treated with much smaller doses of bisphosphonates than the oncology patients,” LeBoff said.
Thirteen of 15 osteoporosis patients were taking oral alendronate (Fosamax, Merck).
Higher rates of osteonecrosis of the jaw in cancer patients can occur because those patients are more commonly treated with IV bisphosphonates, LeBoff said. The data also suggested a time and dose-dependent effect on the risk of osteonecrosis of the jaw, she said.
“What’s happened is that the risk in patients who are getting very high doses for malignancies appears to be different than for those patients who are being treated for osteoporosis or Paget’s disease, where it appears to be an extremely low risk but not zero,” LeBoff said. “It’s very uncommon according to available data and because many physicians who work have large clinical practices in metabolic bone disease are not seeing [osteonecrosis of the jaw] in their patients.”
Although there are many unanswered questions about the incidence, characteristics, etiology, risk factors and treatment approaches, it is important to review the current FDA precaution regarding [osteonecrosis of the jaw] in the patient starting or undergoing treatment with bisphosphonates, he said.
Patients with osteoporosis who take bisphosphonates may develop the condition due to chronic kidney disease, LeBoff said.
“Unlike postmenopausal osteoporosis, fractures in patients with end-stage renal disease may represent one of several types of metabolic bone disease,” LeBoff said.
Such fractures may occur in the setting of secondary parathyroidism, osteomalacia, aluminum-related or adynamic bone disease, LeBoff said.
“Certainly it is important to treat the underlying metabolic disease and not use bisphosphonates until the disorder, calcium homeostasis or other underlying pathophysiology is corrected with existing treatment,” LeBoff said.
According to bone density criteria, osteoporosis is present in 85% of women with renal insufficiency and glomerular filtration rates less than 60 mL/min, LeBoff said. Bisphosphonate use is not recommended in patients with glomerular filtration rates of less than 30 mL/min or 35 mL/min.
For patients with end-stage renal disease and low bone mass on dialysis, a risk of protracted hypercalcemia exists with use of IV bisphosphonates, LeBoff said.
“If one should consider using a bisphosphonate in a patient with end-stage renal disease, it’s important to rule out osteomalacia or adynamic bone disease before starting bisphosphonates,” LeBoff said.
In Woo’s study, osteonecrosis of the jaw occurred primarily in patients taking IV bisphosphonates. But onset occurred after dentoalveolar surgery in 60% of all patients, including those who took oral bisphosphonates.
Patients who take oral bisphosphonates should be advised of a potential osteonecrosis of the jaw risk, according to FDA precautions, LeBoff said.
Although there is a low risk with three or four years oral bisphosophonate use, there is more concern with long-term use, she said.
Patients about to begin bisphosphonate therapy should maintain good dental hygiene and treat oral infections, Woo’s study advised.
For all bisphosphonate users in general, conservative alternatives to surgical procedure and regular dental assessments are advised.
Opting for root canal over extraction is a safer bet, LeBoff said.
“That would be preferred because it’s not an extraction, which has been associated with osteonecrosis of the jaw.”
No randomized data exist that show stopping bisphosphonate therapy several months before dental surgery lowers the risk of osteonecrosis, LeBoff said. Bisphosphonates’ long skeletal retention, as well as other possible mechanisms, has made this difficult to assess, LeBoff said.
People currently diagnosed with osteonecrosis of the jaw should also exercise conservative dental care and find alternatives to surgery. Use of antimicrobial rinses and, in select instances, systemic antibiotics may also be helpful, LeBoff said. – by Rachel Eskenazi
Dr. Leboff has a research grant supported by Novartis and has participated in a roundtable discussion by Proctor and Gamble.
For more information: - LeBoff MS. Controversies in bisphosphonate therapy 2006: Use in renal insufficiency and osteonecrosis of the jaw. Presented at: Endocrine Society’s 88th Annual Meeting; June 25, 2006; Boston.
- Shane E, Goldring S, Christakos S. Osteonecrosis of the jaw: more research needed. J Bone Miner Res. Published online 2006:10.1359/jbmr.060712 (To access, click here).
